Year: 2019
Type: dissertation
Abstract: Brain circuits in complex motor sequencing behavior and speech productionThe uniquely human ability to generate spoken language is one of the most complex movement paradigms in nature.Groups of muscles in the face, larynx (Ziegler and Ackermann, 2013) and tongue (Sanders et al., 2013) must work in concert to produce coherent speech patterns.Fluent production of speech reaches a speed of, on average, 5 syllables per second (Baese-Berk and Morrill, 2015), which necessitates fast coordination of activation and inactivation between these muscle groups.This is different from non-speech oral tasks, which generally are less complex and require lower spatiotemporal coordination of orofacial musculature (Bunton, 2008).In order to understand how such complex motor sequences necessary for speech are generated, we can explore how movement in general is encoded in the brain.Movement, and especially the generation of complex sequences of movement, is governed by the cortico-striato-thalamic circuitry (Doyon et al., 2003).Within this circuitry, movement is initiated in the cortex and activity is sent along downward projections toward the striatum, which in humans consists of the caudate and the putamen.Corticostriatal connections terminate on two major cell classes in the striatum: medium spiny neurons (MSNs) of the striatonigral direct pathway, and MSNs of the striatopallidal indirect pathway.The separation between these pathways and their involvement in the modulation of activity plays a key role in motor control and motor sequence learning (Calabresi et al., 2014).Regulation of striatal activity in these two projection pathways is thought to be highly important for complex motor sequence learning and execution of complex motor tasks, including the production of spoken language (Gracco et al., 2005; Simonyan et al., 2016). The cortico-striato-thalamic circuitCorticostriatal connections are excitatory and activate neurons of both the direct and indirect pathway (Shepherd, 2013).These two striatal cell classes can be distinguished by unique protein expression in addition to their downstream projection patterns (Gittis and Kreitzer, 2012).Direct pathway striatal MSNs express the dopamine 1 receptor (D1R), substance P and dynorphin (D1R-MSNs).By contrast, the indirect pathway MSNs express the dopamine 2 receptor (D2R), enkephalin and A2a adenosine receptors (D2R-MSNs).All striatal MSNs are GABAergic and send inhibitory projections to downstream targets, which ultimately affects activity in the substantia nigra (SNr) (Figure 1a).The direct projection of the D1R-MSNs inhibits the substantia nigra.By contrast, the striatopallidal projections of the D2R-MSNs inhibit the globus pallidus and subthalamic nucleus.Projections from these areas normally inhibit the SNr as well.However, indirect pathway activity modulates the inhibitory drive from these regions by increasing inhibition within the globus pallidus and STN.This way, increased D2R-MSN activity leads to disinhibition of the SNr.Additionally, MSNs are also able to regulate activity within the striatum, as D1R-MSNs and D2R-MSNs project unidirectionally to other D1R-MSNs or DR2-MSNs, respectively (Taverna et al., 2008).Increased activity in D1R-or D2R-MSNs therefore results in a negative feedback loop, which
Source: MPG.PuRe (Max Planck Society)
Author: Jon-Ruben van Rhijn
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2909916132